title: The dual role of filamin A in cancer: can't live with (too much of) it, can't live without it.
abstract: Filamin A (FlnA) has been associated with actin as cytoskeleton regulator. Recently its role in the cell has come under scrutiny for FlnA's involvement in cancer development. FlnA was originally revealed as a cancer-promoting protein, involved in invasion and metastasis. However, recent studies have also found that under certain conditions, it prevented tumor formation or progression, confusing the precise function of FlnA in cancer development. Here, we try to decipher the role of FlnA in cancer and the implications for its dual role. We propose that differences in subcellular localization of FlnA dictate its role in cancer development. In the cytoplasm, FlnA functions in various growth signaling pathways, such as vascular endothelial growth factor, in addition to being involved in cell migration and adhesion pathways, such as R-Ras and integrin signaling. Involvement in these pathways and various others has shown a correlation between high cytoplasmic FlnA levels and invasive cancers. However, an active cleaved form of FlnA can localize to the nucleus rather than the cytoplasm and its interaction with transcription factors has been linked to a decrease in invasiveness of cancers. Therefore, overexpression of FlnA has a tumor-promoting effect, only when it is localized to the cytoplasm, whereas if FlnA undergoes proteolysis and the resulting C-terminal fragment localizes to the nucleus, it acts to suppress tumor growth and inhibit metastasis. Development of drugs to target FlnA and cause cleavage and subsequent localization to the nucleus could be a new and potent field of research in treating cancer.
authors.affiliation: Department of Urology, University of California Davis School of Medicine, University of California, 4860 Y Street, Suite 3500, Sacramento, California 95817, USA VA Northern California Health Care System, Mather, California, USA.
authors.forename: Rosalinda M
authors.initials: RM
authors.lastname: Savoy
authors.forename: Paramita M
authors.initials: PM
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D002273:Carcinogens; D064448:Filamins / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D002273:Carcinogens; D064448:Filamins; D025521:Tumor Suppressor Proteins
keywords: cancer; cytoplasm; filamin A; localization; metastasis; nucleus; transcription